A Center of Research Translation in Psoriasis based at University Hospitals Case Medical Center will integrate a strong psoriasis and skin disease research base with a large existing cohort of psoriasis patients. $5M from the new University Hospitals Murdough Family Center for Psoriasis will further increase the capabilities and geography of the clinical referral network, and in combination with $2M from Case School of Medicine for recruitment in psoriasis, these resources comprise a substantial institutional commitment to the CORT. The Skin Diseases Research Center's cutaneous biology infrastructure and experience will accelerate the Case Psoriasis CORT's advances for psoriasis patient benefit. The translational projects envisioned will test innovative therapeutic interventions in psoriasis that are based upon new mechanistic findings. They also provide new pathogenetic information using biologic samples from patients and animal models. It is intended that each Project will generate therapeutic modalities that change the treatment of psoriasis patients. Project 1 is a novel photodynamic therapy (PDT) Phase I mechanistic, safety, and preliminary efficacy study which also develops a real-time patient-optimized therapy device. Project 2 is a basic study that determines novel roles for S100 proteins in the pathogenesis of psoriasis, including proof-of-principle testing of S100 and macrophage interplay in psoriasis skin on xenogenic transplants. Project 3 takes advantage of a novel transgenic mouse model of psoriasiform dermatitis to examine the potential role of VEGF, S100 A8/9 and vascular changes exacerbating psoriasis. Project 4 explores whether the new clinical finding that psoriasis patients are at higher cardiovascular risk is related to S100 A8/9 overexpression and addresses if aggressive psoriasis treatment directed at S100 serum levels improves cardiovascular risk. The studies will be supported by two project-focused scientific Cores in A) Statistics and B) Systems Biology, and by an Administrative Core. An Advisory Board with representation by both male and female patients, as well as parents, some of whom are also renowned scientists, will oversee the CORT and the P&F review. The CORT will thus bring a multidisciplinary team of translational physician scientists, nurses, community clinicians, laity, and basic scientists from different departments and disciplines together to apply the intellectual and scientific resources of the institution to new therapies for psoriasis patients.